Cardiovascular and Metabolic Effects of High‐dose Insulin in a Porcine Septic Shock Model

• Published in: Academic emergency medicine 2010-04, Vol.17 (4), p.429-435
• Main Authors: Holger, Joel S., Dries, David J., Barringer, Kelly W., Peake, Benjamin J., Flottemesch, Thomas J., Marini, John J.
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure - drug effects; Cardiac Output - drug effects; Cardiovascular system; Cardiovascular System - drug effects; Confidence Intervals; critical care; Disease Models, Animal; Dose-Response Relationship, Drug; Emergency medical care; Heart Rate - drug effects; high‐dose insulin; Hogs; Infusions, Intravenous; Insulin; Insulin - pharmacology; Lactates - metabolism; Metabolism; Myocardial Contraction - drug effects; myocardial depression; Oxygen - blood; Oxygen Consumption - physiology; Probability; Random Allocation; Reference Values; Risk Factors; Sepsis; septic shock; Shock, Septic - drug therapy; Shock, Septic - mortality; Shock, Septic - physiopathology; Survival Rate; Swine; Vascular Resistance - drug effects
• ISSN: 1069-6563; 1553-2712
• DOI: 10.1111/j.1553-2712.2010.00695.x

Objectives:  High‐dose insulin (HDI) has inotropic and vasodilatory properties in various clinical conditions associated with myocardial depression. The authors hypothesized that HDI will improve the myocardial depression produced by severe septic shock and have beneficial effects on metabolic parameters. In an animal model of severe septic shock, this study compared the effects of HDI treatment to normal saline (NS) resuscitation alone. Methods:  Ten pigs were randomized to an insulin (HDI) or NS group. All were anesthetized and instrumented to monitor cardiovascular function. In both arms, Escherichia coli endotoxin lipopolysaccharide (LPS) and NS infusions were begun. LPS was titrated to 20 μg/kg/hour over 30 minutes and continued for 5 hours, and saline was infused at 20 mL/kg/hour throughout the protocol. Dextrose (50%) was infused to maintain glucose in the 60–150 mg/dL range, and potassium was infused to maintain a level greater than 2.8 mmol/L. At 60 minutes, the HDI group received an insulin infusion titrated from 2 to 10 units/kg/hour over 40 minutes and continued at that rate throughout the protocol. Survival, heart rate (HR), mean arterial pressure (MAP), pulmonary artery and central venous pressure, cardiac output, central venous oxygen saturation (SVO2), and lactate were monitored for 5 hours (three pigs each arm) or 7 hours (two pigs each arm) or until death. Cardiac index, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), O2 delivery, and O2 consumption were derived from measured data. Outcomes from the repeated‐measures analysis were modeled using a mixed‐effects linear model that assumed normally distributed errors and a random effect at the subject level. Results:  No significant baseline differences existed between arms at time 0 or 60 minutes. Survival was 100% in the HDI arm and 60% in the NS arm. Cardiovascular variables were significantly better in the HDI arm: cardiac index (p